Radiobiologically derived biphasic fractionation schemes to overcome the effects of tumour hypoxia

Objective: As a fractionated course of radiotherapy proceeds tumour shrinkage leads to resolution of hypoxia and the initiation of accelerated proliferation of radioresistant cancer cells with better repair capacity. We hypothesise that, in tumours with significant hypoxia, improved tumour control could be achieved with biphasic fractionation schedules that either use acceleration after 3–4 weeks of conventional radiotherapy or deliver a higher proportional dose towards the end of a course of treatment. We conducted a modelling study based on the concept of biological effective dose (BED) comparing such novel regimens with conventional fractionation. Methods: The comparator conventional fractionation schedule 70 Gy in 35 fractions delivered over 7 weeks was tested against the following novel regimens, both of which were designed to be isoeffective in terms of late normal tissue toxicity. 40 Gy in 20 fractions over 4 weeks followed by 22.32 Gy in 6 consecutive daily fractions (delayed acceleration) 30.4 Gy in 27 fractions over 4 weeks followed by 40 Gy in 15 fractions over 3 weeks (temporal dose redistribution) The delayed acceleration regimen is exactly identical to that of the comparator schedule over the first 28 days and the BED gains with the novel schedule are achieved during the second phase of treatment when reoxygenation is complete. For the temporal redistribution regimen, it was assumed that the reoxygenation fraction progressively increases during the first 4 weeks of treatment and an iterative approach was used to calculate the final tumour BED for varying hypoxic fractions. Results: Novel fractionation with delayed acceleration or temporal fractionation results in tumour BED gains equivalent to 3.5–8 Gy when delivered in 2 Gy fractions. Conclusion: In hypoxic tumours, novel fractionation strategies result in significantly higher tumour BED in comparison to conventional fractionation. Advances in knowledge: We demonstrate that novel biphasic fractionation regimens could overcome the effects of tumour hypoxia resulting in biological dose escalation.

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Development of a Seabed Geomorphology classification approach; aspiring towards a robust tool to support comprehensive and consistent seabed mapping

10.5194/egusphere-egu21-7751 ◽

2021 ◽

Author(s):

Dayton Dove ◽

Rachel Nanson ◽

Lilja Bjarnadóttir ◽

Janine Guinan ◽

Joana Gafeira ◽

...

Keyword(s):

Classification Scheme ◽

Primary Objective ◽

Second Phase ◽

The Novel ◽

New Classification ◽

British Geological Survey ◽

Origin And Evolution ◽

Initial Application ◽

Seabed Mapping ◽

The Uk

In 2016, through a collaboration between marine mapping programmes in Norway, Ireland, and the UK, we published a new classification scheme to aid the characterisation of seabed geomorphology (Dove et al., 2016). The classification scheme was developed to address shared objectives and challenges in seabed mapping, particularly to enable more consistent classification where required. The novel aspect of this framework was the effort to independently describe seabed features according to their observed physical 1-Morphology, and the more subjective interpretation of their origin and evolution (2-Geomorphology). Initial application of the approach within our own groups and externally proved promising, and through the welcome involvement of colleagues from Geoscience Australia, we continued to progress and improve the approach.We are now within the second phase of the project, which involves the development of glossaries for both parts of the classification scheme. The glossary for part-1 Morphology was recently completed and published (Dove et al., 2020). This glossary includes a revised list of feature names, with definitions and representative diagrams for each feature. Feature definitions are in-part drawn from the International Hydrographic Organization (IHO) guide for undersea feature names, which were modified and augmented with additional terms to ensure the final feature catalogue and glossary encompasses the diversity of morphologies observed at the seabed.Part-2 Geomorphology glossary is now in development. We anticipate it to be more complicated than the Morphology glossary due to the (often) variable meaning of different terms between different fields and individual scientists. But as for Part 1, our primary objective is to produce a useful and robust framework (applicable from the coastal zone to the abyss), that minimises duplication and/or ambiguity as much as possible. The Geomorphology glossary will include example bathymetry images to add further value.Dove, D., Bradwell, T., Carter, G., Cotterill, C., Gafeira Goncalves, J., Green, S., Krabbendam, M., Mellett, C., Stevenson, A., Stewart, H. and Westhead, K., Scott, G., Guinan, J., Judge, M., Monteys, X., Elvenes, S., Maeten, N., Dolan, M., Thorsnes, T., Bjarnadottir, L., Ottesen, D., 2016. Seabed geomorphology: a two-part classification system. British Geological Survey, Open Report OR/16/001.Dove, D., Nanson, R., Bjarnad&#243;ttir, L.R., Guinan, J., Gafeira, J., Post, A., Dolan, M.F.J., Stewart, H., Arosio, R. and Scott, G., 2020. A two-part seabed geomorphology classification scheme:(v. 2). Part 1: morphology features glossary.

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Dose–time fractionation schedules of preoperative radiotherapy and timing to surgery for rectal cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920907537 ◽

2020 ◽

Vol 12 ◽

pp. 175883592090753 ◽

Cited By ~ 1

Author(s):

Fu Jin ◽

Huanli Luo ◽

Juan Zhou ◽

Yongzhong Wu ◽

Hao Sun ◽

...

Keyword(s):

Rectal Cancer ◽

Intensity Modulated Radiotherapy ◽

Clinical Practices ◽

International Consensus ◽

Time To Surgery ◽

Dose Time ◽

Fractionation Schedule ◽

Integrated Boost ◽

Target Volumes ◽

Fractionation Schedules

Chemoradiotherapy (CRT) is extensively used prior to surgery for rectal cancer to provide significantly better local control, but the radiotherapy (RT), as the other component of CRT, has been subject to less interest than the drug component in recent years. With considerable developments in RT, the use of advanced techniques, such as intensity-modulated radiotherapy (IMRT) in rectal cancer, is garnering more attention nowadays. The radiation dose can be better conformed to the target volumes with possibilities for synchronous integrated boost without increased complications in normal tissue. Hopefully, both local recurrence and toxicities can be further reduced. Although those seem to be of interest, many issues remain unresolved. There is no international consensus regarding the radiation schedule for preoperative RT for rectal cancer. Moreover, an enormous disparity exists regarding the RT delivery. With the advent of IMRT, variations will likely increase. Moreover, time to surgery is also quite variable, as it depends upon the indication for RT/CRT in the clinical practices. In this review, we discuss the options and problems related to both the dose–time fractionation schedule and time to surgery; furthermore, it addresses the research questions that need answering in the future.

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Radiotherapy Combined with Other Treatments in Rectal Cancer

Tumori Journal ◽

10.1177/030089169808400223 ◽

1998 ◽

Vol 84 (2) ◽

pp. 238-246 ◽

Cited By ~ 5

Author(s):

Vincenzo Valentini

Keyword(s):

Rectal Cancer ◽

Local Control ◽

Local Control Rate ◽

Bolus Administration ◽

Conventional Fractionation ◽

Fractionation Schedule ◽

Group 5 ◽

The Individual ◽

Improvement In Survival ◽

The Cost

Since the first reports in the late 1950's, a large amount of data have been collected. The analysis of the main evidence from the major randomized trials will be analyzed in this paper according to preoperative, postoperative and chemoradiation approaches. Fifteen randomized preoperative trials were reported; they have been grouped according to the fractionation schedule. In the hypofractionation group (5 Gy for fraction), all five studies that delivered 3-5 doses in one week had a significant improvement in local control and one of them also showed improvement in survival. Operative mortality was higher in the radiotherapy arm if inadequate techniques had been applied. In 3 out of 8 studies with conventional fractionation there was a significant improvement in local control, but no impact in survival was detected. No studies with total dose lower than 34 Gy had an improvement in local control. None of the six randomized postoperative studies showed an improvement in local control or survival. In all trials the local control rate was uniform; ranging from 76% to 84%. Toxicity was higher in the radiotherapy arm. One preoperative and five postoperative randomized studies that used chemoradiation were analyzed. One postoperative chemoradiation study showed a significant improvement in survival in comparison to the surgery arm, and another showed the same advantage compared to the postoperative arm. Protracted infusional administration of 5FU concomitant to radiotherapy showed better survival than bolus administration. No advantages were shown in using MeCCNU or Levamisole in two studies. Toxicity was high and related to the dose and the modality of administration of the drugs in order to adequately treat the different stages of rectal cancer, patients must be carefully selected in order to prescribe the most effective and the least toxic treatment for the individual stage; organ preservation should be an essential goal for its impact on quality of life, and the cost estimates should be taken into account.

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Haemostatic radiotherapy for bleeding cancers of the upper gastrointestinal tract

British Journal of Hospital Medicine ◽

10.12968/hmed.2019.80.10.579 ◽

2019 ◽

Vol 80 (10) ◽

pp. 579-583 ◽

Cited By ~ 1

Author(s):

Christopher Hughes ◽

Ganesh Radhakrishna

Keyword(s):

Case Reports ◽

Meta Analysis ◽

Performance Status ◽

Palliative Radiotherapy ◽

Convincing Evidence ◽

Gastrointestinal Malignancies ◽

Phase 2 Trial ◽

Fractionation Schedule ◽

Fractionation Schedules ◽

Upper Gastrointestinal

Bleeding can cause significant morbidity in patients with upper gastrointestinal malignancies. Palliative radiotherapy can palliate bleeding effectively across numerous cancer sites such as the lung and rectum. The data available regarding the role in bleeding from upper gastrointestinal cancers are limited to a single meta-analysis, a phase 2 trial, eleven retrospective cohorts and two case reports, with the majority focusing on gastric cancer. From the data available radiotherapy appears to be a well-tolerated, effective haemostatic agent that should be considered in all patients with bleeding from an upper gastrointestinal malignancy. Questions remain regarding the radiobiology of haemostasis and the optimum fractionation schedule. There is no convincing evidence that protracted higher dose regimens provide additional benefit. Commonly used fractionation schedules use 1, 5 or 10 fractions. Short fractionation schedules have been used in patients with deteriorating performance status.

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Evaluating occurrence of contaminants of emerging concerns in MF/RO treatment of primary effluent for water reuse – Pilot study

Journal of Water Reuse and Desalination ◽

10.2166/wrd.2019.004 ◽

2019 ◽

Vol 9 (4) ◽

pp. 350-371

Author(s):

Mojtaba Farrokh Shad ◽

Graham J. G. Juby ◽

Saied Delagah ◽

Mohamadali Sharbatmaleki

Keyword(s):

Water Reuse ◽

Polyvinylidene Fluoride ◽

Phase 1 ◽

Settling Tank ◽

Second Phase ◽

The Novel ◽

Inland Empire ◽

Novel Approach ◽

Treatment Train ◽

Ro Concentrate

Abstract This study experimented with the novel approach of using a microfiltration (MF) and reverse osmosis (RO) treatment train to treat the effluent of a primary settling tank at the Inland Empire Utility Agency in Chino, CA. The pilot used polyvinylidene fluoride hollow-fiber MF modules as pretreatment for an RO skid, which used Hydranautics ESPA2 membranes in a two-stage configuration with a feed capacity of 6 gallon per minute (gpm). In this pilot configuration, researchers monitored the removal of 38 most prevalent contaminants of emerging concerns (CECs) through the MF/RO process. To investigate how operating the RO process at two fixed recovery rates of 55% and 80% would affect the performance of the MF/RO membranes, researchers applied different fluxes (8, 10, 12 and 14 gal/d/ft2 (gfd)) and evaluated the removal of CECs in 1-stage and 2-stage RO configurations. The occurrence of CECs in the MF influent, MF effluent, RO permeate, and RO concentrate were analyzed and studied. In the first phase (1-stage the RO process), flux of 14 gfd showed a better rejection value of inorganics (95.2%) when compared with those of other fluxes. Meanwhile, in the second phase (2-stage RO process), flux of 12 gfd showed a better rejection of inorganics (93.7%) when compared with those of other fluxes. Although concentrations of CECs slightly decreased in the RO permeate as the flux has increased, statistical analysis showed no significant differences between different fluxes in terms of CEC rejection.

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A New Meta Heuristic Based Segmentation for MRI Image

Journal of Medical Imaging and Health Informatics ◽

10.1166/jmihi.2020.3048 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1525-1533

Author(s):

R. Meera ◽

P. Anandan ◽

N. Nandhagopal

Keyword(s):

Histogram Equalization ◽

Tumor Segmentation ◽

Second Phase ◽

The Novel ◽

Brain Tumor Segmentation ◽

Brain Images ◽

Low Contrast ◽

Migrating Birds Optimization ◽

Image Pixels ◽

Migrating Birds

An automated brain tumor segmentation and detection have huge importance in the diagnostics of medical field as it renders information about functional structures in addition to the probable abnormal tissue required for surgical planning. However, it is still a problem due to low contrast and poorly-specified boundaries and accuracy issue. Hence, Refined Migrating Birds Optimization (RMBO) algorithm is introduced for automatic tumor segmentation that gets over the disadvantage of classical metaheuristic segmentation techniques. The RMBO helps in improving both migration and position update steps which includes three phases. First phase starts from Preprocessing, film artifacts and unnecessary areas (skull) of MRI images are eliminated with the help of enhanced tracking algorithm. Next and second phase being the procedure of eliminating the noises employing Anisotropic Filtering and contrast enhancement is carried out with the help of histogram equalization. Finally segmentation is performed employing RMBO. The novel algorithm operates on the image pixels information along with regions/neighborhood map to generate a contextual area where the merging is possible. With the RMBO algorithm, MRI of brain images are segmented and the results are analyzed through the comparison of the existing techniques viz., Particle Swarm Optimization (PSO), Genetic algorithms.

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